No Increase in SLE-Related Antibodies Seen on Etanercept

BOSTON — Patients with spondyloarthropathy (SpA) who undergo therapy with the tumor necrosis factor-α inhibitor etanercept are at low risk of developing antibodies associated with systemic lupus erythematosus, according to a poster presentation at the annual meeting of the Federation of Clinical Immunology Societies.

Although these potentially harmful antibodies seem to be increased in patients receiving infliximab, neither of the biologics induced lupus-like symptoms, one of the feared side effects of anti-TNF-α therapy.

Recent studies have shown promising results of anti-TNF-α therapy in patients with SpA. Many more have documented their efficacy in rheumatoid arthritis (RA). But enthusiasm for the new drugs has been muted by widespread concern over side effects that range from headache to infection and lymphoma.

In addition, numerous reports in the RA literature now show that infliximab induces antibodies associated with SLE. But the actual induction of clinically relevant lupus appears to be rare, and tracing its origin to drug-induced TNF-α blockade has been difficult to do.

In a previous study, Leen De Rycke, M.D., and colleagues from Ghent University Hospital, Belgium, reported for the first time that RA and SpA patients taking infliximab tended to produce high levels of the SLE antibodies, antinuclear antibodies (ANAs) and anti-double-stranded DNA (anti-dsDNA) antibodies (Arthritis Rheum. 2003;48:1015–23).

In their new study, they set out to see what happened to these patients over the long term, and whether etanercept therapy induces high antibody responses similar to those of infliximab.

Dr. De Rycke and associates followed 20 SpA patients for 1 year of treatment with etanercept. They compared the number of patients who developed newly induced autoantibodies in this cohort with those of 34 SpA patients who underwent infliximab therapy for 2 years.

On average, patients in the etanercept group were a decade younger (37 years of age) than those in the infliximab group (47 years). Autoimmunity at baseline was low. None of the patients was taking concomitant methotrexate. After 1 year, 10% of the SpA patients on etanercept had evidence of newly induced ANAs compared with 62% of the patients taking infliximab.

Similarly, newly induced anti-dsDNA antibodies were present in the sera of 10% of patients receiving etanercept, and in 71% of those receiving infliximab. Neither drug induced anti-ENA or antihistone antibodies.

Nor did any patients in either group develop lupus-like symptoms. Titers of IgM, but not IgG, anticardiolipin were selectively increased after infliximab but not etanercept therapy. The anti-dsDNA antibodies were predominantly of the immunoglobulin M (IgM) and immunoglobulin G (IgG) isotype. Lupus-associated anti-dsDNA antibodies are classically of the IgG isotope.

“This study indicates that the prominent ANA and anti-dsDNA autoantibody response is not a pure class effect of TNF-α blockers,” Dr. De Rycke and colleagues concluded. Moreover, it “is not associated with clinically relevant lupus symptoms,” they said.

BOSTON — Patients with spondyloarthropathy (SpA) who undergo therapy with the tumor necrosis factor-α inhibitor etanercept are at low risk of developing antibodies associated with systemic lupus erythematosus, according to a poster presentation at the annual meeting of the Federation of Clinical Immunology Societies.

Although these potentially harmful antibodies seem to be increased in patients receiving infliximab, neither of the biologics induced lupus-like symptoms, one of the feared side effects of anti-TNF-α therapy.

Recent studies have shown promising results of anti-TNF-α therapy in patients with SpA. Many more have documented their efficacy in rheumatoid arthritis (RA). But enthusiasm for the new drugs has been muted by widespread concern over side effects that range from headache to infection and lymphoma.

In addition, numerous reports in the RA literature now show that infliximab induces antibodies associated with SLE. But the actual induction of clinically relevant lupus appears to be rare, and tracing its origin to drug-induced TNF-α blockade has been difficult to do.

In a previous study, Leen De Rycke, M.D., and colleagues from Ghent University Hospital, Belgium, reported for the first time that RA and SpA patients taking infliximab tended to produce high levels of the SLE antibodies, antinuclear antibodies (ANAs) and anti-double-stranded DNA (anti-dsDNA) antibodies (Arthritis Rheum. 2003;48:1015–23).

In their new study, they set out to see what happened to these patients over the long term, and whether etanercept therapy induces high antibody responses similar to those of infliximab.

Dr. De Rycke and associates followed 20 SpA patients for 1 year of treatment with etanercept. They compared the number of patients who developed newly induced autoantibodies in this cohort with those of 34 SpA patients who underwent infliximab therapy for 2 years.

On average, patients in the etanercept group were a decade younger (37 years of age) than those in the infliximab group (47 years). Autoimmunity at baseline was low. None of the patients was taking concomitant methotrexate. After 1 year, 10% of the SpA patients on etanercept had evidence of newly induced ANAs compared with 62% of the patients taking infliximab.

Similarly, newly induced anti-dsDNA antibodies were present in the sera of 10% of patients receiving etanercept, and in 71% of those receiving infliximab. Neither drug induced anti-ENA or antihistone antibodies.

Nor did any patients in either group develop lupus-like symptoms. Titers of IgM, but not IgG, anticardiolipin were selectively increased after infliximab but not etanercept therapy. The anti-dsDNA antibodies were predominantly of the immunoglobulin M (IgM) and immunoglobulin G (IgG) isotype. Lupus-associated anti-dsDNA antibodies are classically of the IgG isotope.

“This study indicates that the prominent ANA and anti-dsDNA autoantibody response is not a pure class effect of TNF-α blockers,” Dr. De Rycke and colleagues concluded. Moreover, it “is not associated with clinically relevant lupus symptoms,” they said.

BOSTON — Patients with spondyloarthropathy (SpA) who undergo therapy with the tumor necrosis factor-α inhibitor etanercept are at low risk of developing antibodies associated with systemic lupus erythematosus, according to a poster presentation at the annual meeting of the Federation of Clinical Immunology Societies.

Although these potentially harmful antibodies seem to be increased in patients receiving infliximab, neither of the biologics induced lupus-like symptoms, one of the feared side effects of anti-TNF-α therapy.

Recent studies have shown promising results of anti-TNF-α therapy in patients with SpA. Many more have documented their efficacy in rheumatoid arthritis (RA). But enthusiasm for the new drugs has been muted by widespread concern over side effects that range from headache to infection and lymphoma.

In addition, numerous reports in the RA literature now show that infliximab induces antibodies associated with SLE. But the actual induction of clinically relevant lupus appears to be rare, and tracing its origin to drug-induced TNF-α blockade has been difficult to do.

In a previous study, Leen De Rycke, M.D., and colleagues from Ghent University Hospital, Belgium, reported for the first time that RA and SpA patients taking infliximab tended to produce high levels of the SLE antibodies, antinuclear antibodies (ANAs) and anti-double-stranded DNA (anti-dsDNA) antibodies (Arthritis Rheum. 2003;48:1015–23).

In their new study, they set out to see what happened to these patients over the long term, and whether etanercept therapy induces high antibody responses similar to those of infliximab.

Dr. De Rycke and associates followed 20 SpA patients for 1 year of treatment with etanercept. They compared the number of patients who developed newly induced autoantibodies in this cohort with those of 34 SpA patients who underwent infliximab therapy for 2 years.

On average, patients in the etanercept group were a decade younger (37 years of age) than those in the infliximab group (47 years). Autoimmunity at baseline was low. None of the patients was taking concomitant methotrexate. After 1 year, 10% of the SpA patients on etanercept had evidence of newly induced ANAs compared with 62% of the patients taking infliximab.

Similarly, newly induced anti-dsDNA antibodies were present in the sera of 10% of patients receiving etanercept, and in 71% of those receiving infliximab. Neither drug induced anti-ENA or antihistone antibodies.

Nor did any patients in either group develop lupus-like symptoms. Titers of IgM, but not IgG, anticardiolipin were selectively increased after infliximab but not etanercept therapy. The anti-dsDNA antibodies were predominantly of the immunoglobulin M (IgM) and immunoglobulin G (IgG) isotype. Lupus-associated anti-dsDNA antibodies are classically of the IgG isotope.

“This study indicates that the prominent ANA and anti-dsDNA autoantibody response is not a pure class effect of TNF-α blockers,” Dr. De Rycke and colleagues concluded. Moreover, it “is not associated with clinically relevant lupus symptoms,” they said.